The In Vitro Actions Of Loxapine On Dopaminergic And Serotonergic Receptors. Time To Consider Atypical Classification Of This Antipsychotic Drug?

Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action.Materials and Methods: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D-1 to D-5 to 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [C-11]-Raclopride [F-18]-Altanserin [F-18]-MPPF [C-11]-SB207145, and [F-18]-2PNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate.Results: In cell cultures, the measured Kb confirmed high affinity of loxapine for the D 2 ; intermediate affinity for the D-1, D-4, D-5, 5-HT2c receptorsl and a lack of affinity toward D-3, 5-HT1A, 5-HT4, 5-HT6 and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D-2 and 5-HT2A receptorsConclusion: This preclinical study reveals that loxapine receptorial spectrum is close to an "atypical" profile (D-2/5HT(2A), ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification.